1. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation1 Target selection – map formation Raghav Rajan Bio 334 – Neurobiology I September 19th 2013

2. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation2 Assignment on disorders ● 1 page write-up – in layman language ● Description of disorder ● Present understanding of the cause? ● What does this tell us about the brain? ● Caveats ● Descriptions are good ● Language not lay enough ● Interpretation, caveats, etc. - largely missing

3. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation3 Example - Synesthesia ● Our sense organs provide us with information about the world around us. Each sense provides us with a different picture of the world. Normally the senses don't overlap ● Just like sensory modalities, we also have categories for concepts like numbers, letters, etc. These are also represented in distinct regions of the brain ● Sometimes, a stimulus that normally only activates one sensory modality (or a particular category) involuntarily activates another sensory modality (or category) ● eg: a particular number or letter is also associated with a particular colour

4. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation4 Quote from a person with number colour synesthesia "A few years ago, I mentioned to a friend that I remembered phone numbers by their colour. He said "So you're a synesthete!" I hadn't heard of synesthesia (which means something close to 'sense-fusion') – I only knew that numbers seemed naturally to have colours: five is blue, two is green, three is red… And music has colours too: the key of C# minor is a sharp, tangy yellow, F major is a warm brown..."[10][10]

5. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation5 Causes of number colour synesthesia ● Not clear ● Seems to be present from childhood in most cases ● Few cases where it seems to have come about through association – for example through refrigerator magnets ● But most cases, it is present without any learning ● Maybe because of extra connections between the colour and number area ● Some evidence that it runs in families ● Can also be induced by drugs, stroke, etc.

6. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation6 Interpretation, future research... ● Some commonalities of synesthetic experience suggests that even abstract concepts like numbers may be represented in the same place and same way across individuals ● Suggests that wiring in the young brain may be more widespread and non-specific ● Pruning of extra connections may happen as the brain matures ● Although since it occurs after drugs, it might even be just a case of the balance between excitation and inhibition ● Two aspects of connectivity – anatomical vs. functional ● More studies on specificity of responses of a particular brain region to one sensory modality

7. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation7 Connecting up with the right cells – networking! ● End result – very well organized maps Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

8. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation8 Neurotrophins and their receptors can help axons choose the right targets ● Typically neurotrophins expressed by the target region ● Receptors expressed by the navigating axons ● Considerable number of different neurotrophins ● Nobel prize – Rita Levi Montalcini, Stanley Cohen (1986) Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

9. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation9 Dendritic target selection based on neurotrophic cues in the inner ear ● Dendrites of all cells express receptors for both NT-3 and BDNF ● Early growth is independent of neurotrophic cues ● BDNF can replace NT-3 with some excess innervation ● Neurotrophins also promote growth and survival Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

10. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation10 In the absence of their normal targets, axons will innervate neighbouring targets... ● LGN degenerates after ablation of visual cortex ● Superior colliculus lesioned Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

11. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation11... except, as always, border patrols try to control infiltration ● Presence of normal axons ● Presence of molecular cues ● All these prevent infiltration ● They also serve to keep axons inside the target area Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

12. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation12 Such erroneous connections can retune cortical areas to reflect properties of the input ● Orientation selective columns appear in rewired ferret A1 ● Some differences with such columns in V1 http://web.mit.edu/msur/www/publications/induction.pdf

13. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation13 Can rewired auditory cortex see the light? ● Animals trained to get reward on the left for a sound stimulus ● Reward on the right for a visual stimulus ● Trained with visual stimuli only in the left visual field ● Tested wit h visual stimuli in the right visual field http://web.mit.edu/msur/www/publications/visual.pdf

14. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation14 More about the methods ● After training, they were tested with light on the right visual field ● They can respond with left V1 or left A1 ● So next, left V1 was ablated ● And finally, left A1 was also ablated http://web.mit.edu/msur/www/publications/visual.pdf

15. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation15 Auditory cortex sees (NOT HEARS) the light http://web.mit.edu/msur/www/publications/visual.pdf

16. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation16 After reaching the target area, very nice topographical maps form ● Visual system topography organized by location in space ● Olfactory system topography organized by receptor type expression Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

17. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation17 Again molecular cues – could be intrinsic to the cell or area that it projects to (or both) ● Rotating the retina does not change the projection topography ● But changes behavior Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

18. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation18 And also experience can change wiring ● Extra whisker at birth results in extra column in S1 ● Missing whisker results in missing column ● Tying two whiskers together results in merged columns Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6

19. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation19 Summary ● A number of molecular cues help axons/dendrites reach the correct targets ● They also help keep them in the target area after they have reached ● Also correct innervation appears to compete and prevent incorrect innervation ● Caveat – incorrect innervation need not be detrimental, but in fact can still sustain correct behavior ● Activity and plasticity influence wiring to a great extent

20. 19th September 2013Bio 334 - Neurobiology I - Target selection - map formation20 Midsem exam ● Application oriented questions ● Read the chapters listed in my lectures and read my lectures ● Some multiple choice questions ● Some short essay type questions – like the disorders assignment ● Good luck!!